ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.3625A>G (p.Thr1209Ala) (rs41281314)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV000787989 SCV000927017 benign Usher syndrome 2019-05-28 reviewed by expert panel curation The filtering allele frequency (the lower threshold of the 95% CI of 3442/23972) of the c.3625A>G (p.Thr1209Ala) variant in the CDH23 gene is 13.15% for African chromosomes by gnomAD, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). A splicing assay did not show any impact to splicing but BS3 was not applied given no assessment of protein function (PMID:18273900). Computational prediction analysis using the metapredictor tool REVEL did not predict an impact the protein (BP4). Of note, this variant was reported in 3 patients with Usher syndrome (PMID: 15537665, 15660226, 12075507) though without any convincing evidence for pathogenicity (PM3 not met). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel : BA1, BS3_Supporting, BP4.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039159 SCV000062843 benign not specified 2010-09-03 criteria provided, single submitter clinical testing Thr1209Ala in exon 31 of CDH23: This variant has been identified in over 20% of a Black population (dbSNP rs41281314) and is therefore classified as benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000039159 SCV000332788 benign not specified 2015-07-10 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000263856 SCV000363712 likely benign Deafness, autosomal recessive 12 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx RCV000039159 SCV000730521 benign not specified 2017-11-03 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics Inc RCV000086973 SCV000841480 benign not provided 2018-05-23 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000039159 SCV001156877 benign not specified 2018-08-31 criteria provided, single submitter clinical testing
OMIM RCV000005210 SCV000025387 uncertain significance Usher syndrome type 1D 2011-01-12 no assertion criteria provided literature only
NEI Ophthalmic Genomics Laboratory,National Institutes of Health RCV000086973 SCV000119226 not provided not provided no assertion provided not provided
GeneReviews RCV000217147 SCV000268755 pathogenic Usher syndrome type 1 2016-05-19 no assertion criteria provided literature only

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